期刊
CELLS
卷 11, 期 14, 页码 -出版社
MDPI
DOI: 10.3390/cells11142249
关键词
acute myeloid leukemia; CD47; immune checkpoint inhibitors; myelodysplastic syndromes; TIM-3
类别
Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many solid tumors, with limited progress made in the area of myeloid malignancies. The low mutational burden of acute myeloid leukemia (AML) is one potential reason behind the lack of activity of T-cell harnessing ICIs, particularly CTLA-4 and PD-1 inhibitors. Innate immune checkpoints play a critical role in the immune escape of AML and myelodysplastic syndromes (MDS). The CD47 targeting agent, magrolimab, has shown promising activity when combined with azacitidine in early phase trials conducted in AML and higher-risk MDS, especially among patients harboring a TP53 mutation. Similarly, sabatolimab (an anti-TIM-3 monoclonal antibody) plus hypomethylating agents have shown durable responses in higher-risk MDS and AML in early clinical trials. Randomized trials are currently ongoing to confirm the efficacy of these agents. In this review, we will present the current progress and future directions of immune checkpoint inhibition in AML and MDS.
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